Single center experience with alpelisib-fulvestrant in heavily pretreated women with HR(+), HER-2 (−) metastatic breast cancer.

e13034 Background: HR-positive, Her2-negative metastatic breast cancer patients harboring PIK3CA mutations are associated with resistance to endocrine therapy and worse prognosis. Results from the phase III SOLAR-1 trial demonstrate improved PFS for patients treated with Alpelisib-Fulvestrant after failure on first or second line treatment with aromatase inhibitor. Methods: Within an early access program for Alpelisib in a single oncology center, patients diagnosed with metastatic HR-positive, Her2 -negative breast cancer were screened for PIK3CA mutations. New generation sequencing (NGS) was the preferred technique to identify carriers with PIK3CA mutations on soft tissue or liquid biopsy. Patients who progressed and carried PIK3CA mutations received Alpelisib and fulvestrant as subsequent line of therapy. Results: Among 32 patients (pts) screened, 13 (40,6%) had a PIK3CA mutation. In total, 11 pts received alpelisib. Median age at diagnosis was 57.5 years (range, 39-69). Eight pts (72.7%) had been operated for early-stage breast cancer, 6 (54.5%) had received adjuvant chemotherapy and 5 (45.5%) had received adjuvant radiotherapy. Of 11 pts with evaluable histology, 3 pts (27.3%) had high grade tumors at diagnosis. Ten pts (90.9%) had PR positive tumors. Median Ki67 was 20% (range, 2-80). Eight pts (72.7%) had PIK3CA exon 20 and 3 (27.3%) had exon 9 mutations. Six pts (54.5%) had received prior chemotherapy in the metastatic setting and 10 (90.9%) prior CDK4/6 inhibitor. Three pts (27.3%) received Alpelisib as 2nd line and all remaining patients received alpelisib beyond 3rd line treatment. All pts (100%) had metastasis to the bones, 8 pts (72.7%) to the liver, 6 pts (54.5%) to the lungs and 2 pts (18.2%) to the brain. Until the date of last assessment, Alpelisib was administered for a median of 5.1 months (range, 0.4-21.3). Ten pts were evaluable for response to treatment with Alpelisib. One (10%) had CR, 5 (50%) SD and 4 (40%) PD as best response. Median duration of disease control was not reached. Baseline characteristics were not associated with disease control. Adverse events noticed were thrombocytopenia grade II (1/11), diarrhea grade II (2/11), skin rash grade I &II (4/11), weakness grade III (1/11) and hyperglycemia (3/11). Conclusions: Prevalence of PIK3CA mutations is consistent with published data. Furthermore, combination of Alpelisib-Fulvestrant is a highly active line of therapy even in heavily pretreated patients.